T-lymphocyte perturbation following large-scale apheresis and hematopoietic stem cell transplantation in HIV-infected individuals

• Published in: Clinical immunology (Orlando, Fla.) Vol. 144; no. 2; pp. 159 - 171
• Main Authors: Savkovic, Borislav, Macpherson, Janet L., Zaunders, John, Kelleher, Anthony D., Knop, Alison E., Pond, Susan, Evans, Louise, Symonds, Geoff, Murray, John M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.08.2012; Elsevier
• Subjects: Allergy and Immunology; Apheresis; Biological and medical sciences; Blood Component Removal; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Death - immunology; Compartment model; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte-colony stimulating factor; Hematopoietic Stem Cell Transplantation; HIV; HIV Infections - immunology; HIV Infections - therapy; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Lymphocyte Activation - immunology; Lymphocyte Count; Lymphocyte distribution and trafficking; Medical sciences; Models, Theoretical; Phenotype; Stem cell transplantation; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; PB; SSE; HIV; Lymphocyte distribution and trafficking; Apheresis; OZ1; LT; Compartment model; Stem cell transplantation; HSC; Granulocyte-colony stimulating factor; G-CSF; Lymph tissue; Granulocyte colony stimulating factor; Hematopoietic stem cell; Peripheral blood; tat–vpr specific anti-HIV ribozyme; Sum-of-squares error; Immunopathology; Stem cell; Retroviridae; Hematopoietic cell; AIDS; Immune deficiency; Lentivirus; Colony stimulating factor; Infection; Virus; Immunology; Granutocyte-colony stimulating factor; Viral disease; Distribution; T-Lymphocyte; Models; Human immunodeficiency virus; Cell migration; Hematopoietic stem cell transplantation
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2012.06.004

Analysis and mathematical modeling of T-lymphocyte perturbation following administration of granulocyte colony stimulating factor (G-CSF) and two large-scale aphereses are reported. 74 HIV-1 positive antiretroviral-treated individuals were infused with gene- or sham-transduced CD34+ hematopoietic stem cells (HSC) in a Phase II clinical trial. T cell numbers were examined in four phases: 1) during steady state; 2) increases in peripheral blood (PB) following G-CSF administration; 3) depletion post-aphereses and 4) reconstitution post HSC infusion. The present analysis provides the first direct estimate of CD4+ T cell distribution and trafficking in HIV-infected individuals on stable HAART, indicating that CD4+ T lymphocytes in PB represent 5.5% of the pool of CD4+ T lymphocytes that traffic to PB. ► We estimate T lymphocyte distribution and trafficking in HIV-infected subjects. ► We perform mathematical modeling on in-vivo T lymphocyte data. ► Our data is from a recent Phase II clinical trial of an anti-HIV gene therapy. ► We find that CD4+ T cells in peripheral blood represent 5.5% of total CD4+ T cells. ► We provide the first direct in-vivo estimate of T cell distribution during HIV.